The aim of the studies contemplated for the period Oct. 1973--Sept. 1974 is to continue the analysis of the anaphylactic process in the guinea pig atrium and to test these findings on surviving preparations of human cardiac tissues. In the guinea pig this will include studies of stored and anaphylactically releasable mediators as they are influenced by sex hormones in castrated and intact animals of both sexes; further, the work will deal with agents known to modulate the level of cyclic AMP in hearts whose anaphylactic reaction sequence has been compromised by heating. In selected cases the tissue levels of this nucleotide will be determined and the effects of steroids on the membrane events will be studied electrophysiologically. The work on human tissues will first comprise an analysis of mediator release by immune complexes in order to establish a corpus of basic information affecting the ensemble of releasable materials. Studies will then be undertaken of the effects of antibody concentration and temperature to obtain values for the energetics of anaphylactic mediator liberation in man. This will be a precondition for the subsequent studies of the biochemical factors underlying the electrophysiological and contractile changes seen in cardiac anaphylaxis. The latter will include measurements of the elastic modulus before and after heating in "normal" and steroid-primed animals, and an investigation of the force-length relationships to detect possible change in the contractile machinery and in excitation-contraction coupling.